[54111-85-2] · C11H16CuLiO2 · Lithium a-Ethoxycarbonylvinyl(1-hexynyl)cuprate · (MW 250.76)
(organometallic reagent for the introduction of an acrylate unit onto allylic halides, vinyl epoxides, and carbonyl compounds; also effective for the synthesis of a-methylene-g-butyrolactones from allylic halides)
Physical Data: thermally unstable organocuprate generated at -78 °C in the absence of moisture and oxygen.
Solubility: sol diethyl ether and THF at temperatures approaching -78 °C.
Preparative Methods: generated at -78 °C in ether by the metal-halogen exchange reaction of ethyl a-bromoacrylate and lithium 1-hexynyl(methyl)cuprate.1
Handling, Storage, and Precautions: must be prepared in the absence of moisture and oxygen at -78 °C. Diethyl ether should be freshly distilled from lithium aluminum hydride. Reaction temperatures should be maintained below -60 °C.
In general, a-alkoxycarbonylvinylic cuprates have been generated in situ from the conjugate additions of organocopper reagents to alkynic esters and acids.2-4 The unsubstituted title reagent can best be prepared by the reaction of methylcuprates with ethyl a-bromoacrylate (eq 1).1 This metal-halogen exchange was first observed by Klein and Levene for substituted a-alkoxycarbonylvinylcuprates.5 While oxidation, protonation, and iodination of the vinylcuprates have met with success, alkylations with simple alkyl halides other than methyl iodide have not been reported.4
The parent a-ethoxycarbonylvinylcuprate selectively reacts with allyl halides and propargyl halides to produce 1,3-dienes (2) and 1,3-enynes (eq 2).1 The adduct (3) of the title reagent with 3-bromocyclohexene produces the acrylic acid (4) after basic hydrolysis (eq 3). Iodolactonization of acid (4) and subsequent deiodination with Tri-n-butylstannane yields the a-methylene-g-butyrolactone (6) (eq 4).1
An application of cuprate (1) in the synthesis of swazinecic acid dilactone6 is provided in eq 5 for the allylation of halide (7).
By analogy to reagent (1), a-methoxycarbonylvinylcuprate (8) was prepared from methyl a-bromoacrylate according to the aforementioned procedure.1 A study of the reactivity of reagent (8) with ketones and a,b-unsaturated ketones was carried out. Unlike most organocuprates, reagent (8) added in a 1,2-manner to the carbonyl group of a series of cyclic ketones at -78 °C in high yield (eq 6).7
More unusual is the fact that cuprate (8) preferentially adds 1,2 and not 1,4 to a variety of enones.7 Cyclohexenone, cyclohexenecarbaldehyde, and acylcyclohexenes all gave 1,2-adducts exclusively with cuprate (8) (eqs 7 and 8). Only the reaction of (8) with methyl vinyl ketone resulted in the 1,4-adduct being the major product (eq 9).
This reactivity profile suggested that the a-alkoxycarbonylvinylcuprates are structurally indicative of an allenoate species. Evidence for the allenoate-type structure (9) comes from IR data5 and trapping of substituted a-alkoxycarbonylvinylcuprates generated in the conjugate addition of alkylcuprates to ethyl propiolate (eq 10).8 After the addition of Lithium Dimethylcuprate to ethyl propiolate at -78 °C, the reaction mixture was quenched with Chlorotrimethylsilane in triethylamine. The O-silylated allene (10) was isolated and characterized by IR and NMR.
Joseph P. Marino & David P. Holub
University of Michigan, Ann Arbor, MI, USA